tbuckley/cabot-search huggingface dataset:
Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials
Authors: F. André, F. Su, N. Solovieff, G. Hortobagyi, S. Chia, P. Neven, A. Bardia, D. Tripathy, Y.-S. Lu, A. Lteif, T. Taran, N. Babbar, D. Slamon, C.L. Arteaga
Journal: Annals of Oncology (2023)

The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib.Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing. An analysis of correlation between gene alteration status and progression-free survival (PFS) was carried out to identify potential biomarkers of response to ribociclib.Multiple frequently altered genes were identified. Alterations in ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 were associated with a greater PFS benefit with ribociclib versus placebo. Patients with high tumour mutational burden (TMB) and with ANO1, CDKN2A/2B/2C, and RB1 alterations exhibited decreased sensitivity to ribociclib versus placebo.Although exploratory, these results provide insight into alterations associated with the improved response to ribociclib treatment and may inform treatment sequencing in patients with actionable alterations following progression on CDK4/6 inhibitors. Validation of potential biomarkers identified here and development of prospective trials testing their clinical utility are warranted.NCT01958021, NCT02422615, NCT02278120.
Ultra-efficient radio-immunotherapy for reprogramming the hypoxic and immunosuppressive tumor microenvironment with durable innate immune memory
Authors: Jichun Yang, Chong Zhang, Xiaohui Chen, Daijun Zhou, Zixin Sun, Ruyan Niu, Ying Zhu, Hengyi Chen, Liu Wang, Yi Chen, Yuhan Wang, Yunqian Fu, Ningyu Ma, Jianjun Li, Yang Luo
Journal: Biomaterials (2023)
The 100 Days Mission: how a new medical-countermeasures network can deliver equity and innovation
Authors: Victor Dzau, Soumya Swaminathan, Charlotte Baker, Rick A Bright, Jose Castillo, Tan Chorh Chuan, Ruxandra Draghia-Akli, Ranna Eardley-Patel, George F Gao, Ken Ishii, Yenew Kebede Tebeje, Teresa Lambe, Shingai Machingaidze, John-Arne Røttingen, Umesh Shaligram, Mariângela Simão, Renu Swarup, Jean-Francois Toussaint, Niteen S Wairagkar
Journal: The Lancet (2023)
Formation and Investigation of Cell‐Derived Nanovesicles as Potential Therapeutics against Chronic Liver Disease
Authors: Aymar Abel Ganguin, Ivo Skorup, Sebastian Streb, Alaa Othman, Paola Luciani
Journal: Advanced Healthcare Materials (2023)

A new therapeutic approach using cell-derived nanovesicles (cdNVs) is offered here to overcome the lack of effective treatments for liver fibrosis, a reversible chronic liver disease. To achieve this goal the formation and purification of cdNVs from untreated, quiescent-like, or activated LX-2 cells, an immortalized human hepatic stellate cell (HSC) line with key features of transdifferentiated HSCs are established. Analysis of the genotype and phenotype of naïve and transdifferentiated LX-2 cells activated through transforming growth factor beta 1, following treatment with cdNVs, reveals a concentration-dependent fibrosis regression. The beneficial fibrosis-resolving effects of cdNVs are linked to their biomolecular corona. Liposomes generated using lipids extracted from cdNVs exhibit a reduced antifibrotic response in perpetuated LX-2 cells and show a reduced cellular uptake. However, incubation with soluble factors collected during purification results in a new corona, thereby restoring fibrosis regression activity. Overall, cdNVs display encouraging therapeutic properties, making them a promising candidate for the development of liver fibrosis resolving therapeutics.
LIM domain only 7 negatively controls non-alcoholic steatohepatitis in the setting of hyperlipidaemia
Authors: Tiangen Wu, Xi Chen, Kequan Xu, Caixia Dai, Xiaomian Li, Yang-Wen-Qing Zhang, Jinghua Li, Meng Gao, Yingyi Liu, Fusheng Liu, Xutao Zhang, Bicheng Wang, Peng Xia, Zhen Li, Weijie Ma, Yufeng Yuan
Journal: Hepatology (2023)

Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms.
Lack of complete biochemical response in autoimmune hepatitis leads to adverse outcome: First report of the IAIHG retrospective registry
Authors: Charlotte D. Slooter, Floris F. van den Brand, Ana Lleo, Francesca Colapietro, Marco Lenzi, Paolo Muratori, Nanda Kerkar, George N. Dalekos, Kalliopi Zachou, M. Isabel Lucena, Mercedes Robles-Díaz, Daniel E. Di Zeo-Sánchez, Raúl J. Andrade, Aldo J. Montano-Loza, Ellina Lytvyak, Birgit I. Lissenberg-Witte, Patrick Maisonneuve, Gerd Bouma, Guilherme Macedo, Rodrigo Liberal, Ynto S. de Boer
Journal: Hepatology (2023)

Background and Aims: The International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of autoimmune hepatitis (AIH). As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort. Methods: This retrospective, observational, multicenter study included all patients with a clinical diagnosis of AIH from the IAIHG-RR. The quality assessment consisted of external validation of completeness and consistency for 29 predefined variables. Cox regression was used to identify risk factors for liver-related death and liver transplantation (LT). Results: This analysis included 2559 patients across 7 countries. In 1700 patients, follow-up was available, with a completeness of individual data of 90% (range: 30–100). During a median follow-up period of 10 (range: 0–49) years, there were 229 deaths, of which 116 were liver-related, and 143 patients underwent LT. Non-White ethnicity (HR 4.1 95% CI: 2.3–7.1), cirrhosis (HR 3.5 95% CI: 2.3–5.5), variant syndrome with primary sclerosing cholangitis (PSC) (HR 3.1 95% CI: 1.6–6.2), and lack of complete biochemical response within 6 months (HR 5.7 95% CI: 3.4–9.6) were independent prognostic factors. Conclusions: The IAIHG-RR represents the world’s largest AIH cohort with moderate-to-good data quality and a relevant number of liver-related events. The registry is a suitable platform for patient selection in future studies. Lack of complete biochemical response to treatment, non-White ethnicity, cirrhosis, and PSC-AIH were associated with liver-related death and LT.
Spatiotemporally‐Programmed Dual‐Acid‐Sensitive Nanoworms of Albumin‐Poly(tertiary amine)‐Doxorubicin Conjugates for Enhanced Cancer Chemotherapy
Authors: Wenchao Huang, Longshuai Zhang, Jiawei Sun, Yuanzi Sun, Like Gong, Sisi Ge, Xunbin Wei, Weiping Gao
Journal: Advanced Healthcare Materials (2023)

Nanomedicines are potentially useful for targeted cancer chemotherapy; however, it is difficult to design nanomedicines with controllable structures and functions to overcome a series of biological and pathological barriers to efficiently kill cancer cells in vivo. Here, this work reports in situ growth of dual-acid-sensitive poly(tertiary amine)-doxorubicin conjugates from albumin to form dual-acid-sensitive albumin-poly(tertiary amine)-doxorubicin conjugates that self-assemble into nanospheres and nanoworms in a controlled manner. Both nanospheres and nanoworms rapidly dissociate into positively-charged unimers at pH < 6.9 and quickly releases the conjugated drug of doxorubicin at pH < 5.6, leading to enhanced penetration in tumor cell spheroids as well as improved uptake and cytotoxicity to tumor cells at pH < 6.9. Notably, nanoworms are less taken up by endothelial cells than nanospheres and doxorubicin, leading to improved pharmacokinetics. In a mouse model of triple negative breast cancer, nanoworms accumulate and penetrate into tumors more efficiently than nanospheres and doxorubicin, leading to enhanced tumor accumulation and penetration. As a result, nanoworms outperform nanospheres and doxorubicin in suppressing tumor growth and elongating the animal survival time, without observed side effects. These findings demonstrate that intelligent nanoworms with spatiotemporally programmed dual-acid-sensitive properties are promising as next-generation nanomedicines for targeted cancer chemotherapy.
Expansion of Anticomplement Therapy Indications from Rare Genetic Disorders to Common Kidney Diseases
Authors: Takashi Miwa, Sayaka Sato, Madhu Golla, Wen-Chao Song
Journal: Annual Review of Medicine (2023)

Complement constitutes a major part of the innate immune system. The study of complement in human health has historically focused on infection risks associated with complement protein deficiencies; however, recent interest in the field has focused on overactivation of complement as a cause of immune injury and the development of anticomplement therapies to treat human diseases. The kidneys are particularly sensitive to complement injury, and anticomplement therapies for several kidney diseases have been investigated. Overactivation of complement can result from loss-of-function mutations in complement regulators; gain-of-function mutations in key complement proteins such as C3 and factor B; or autoantibody production, infection, or tissue stresses, such as ischemia and reperfusion, that perturb the balance of complement activation and regulation. Here, we provide a high-level review of the status of anticomplement therapies, with an emphasis on the transition from rare diseases to more common kidney diseases.
Shearing of surface mucin saps tumor cell strength
Authors: Liza J. Greenberg, Deborah Fass
Journal: Trends in Pharmacological Sciences (2023)

Aberrant expression of transmembrane mucins promotes tumor progression and interferes with immunological and medicinal elimination of cancer cells. In a recent article, Pedram et al. directed an attenuated bacterial mucin-specific protease to HER2-positive tumor cells and observed decreased tumor growth rates and extended survival of mice bearing HER2-positive tumors.
A Zwitterionic Hydrogel with Anti‐Oxidative and Anti‐Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial‐Mesenchymal Transition
Authors: Qingyu Yu, Hong Sun, Linhua Zhang, Lijie Jiang, Lei Liang, Chaojie Yu, Xiaoru Dong, Bingyan Guo, Yuwei Qiu, Jingwu Li, Hong Zhang, Fanglian Yao, Dunwan Zhu, Junjie Li
Journal: Advanced Healthcare Materials (2023)

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-β). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.
Hepatic steatosis aggravates atherosclerosis via small extracellular vesicle-mediated inhibition of cellular cholesterol efflux
Authors: Xu Chen, Shen Chen, Juan Pang, Rong Huang, Yiran You, Haoyang Zhang, Jinghe Xiao, Hongliang Xue, Wenhua Ling
Journal: Journal of Hepatology (2023)
Global Variations According to Sex in Patients Hospitalized for Heart Failure in the REPORT-HF Registry
Authors: Jasper Tromp, Justin A. Ezekowitz, Wouter Ouwerkerk, Chanchal Chandramouli, Kai Hang Yiu, Christiane E. Angermann, Ulf Dahlstrom, Georg Ertl, Mahmoud Hassanein, Sergio V. Perrone, Mathieu Ghadanfar, Anja Schweizer, Achim Obergfell, Kenneth Dickstein, Sean P. Collins, Gerasimos Filippatos, John G.F. Cleland, Carolyn S.P. Lam
Journal: JACC Heart Failure (2023)
Pegylated interferon-α for chronic hepatitis B … not ready to be shelved yet! New insights on its role using single-cell transcriptomics
Authors: Upkar S. Gill, Dimitra Peppa
Journal: Hepatology (2023)

Pegylated-Interferon alpha (PegIFN-α) is a treatment option for chronic hepatitis B (CHB) but has limited efficacy. It has both immune modulatory and antiviral capacity, however the mechanisms of PegIFN-α in relation to CHB pathogenesis remain understudied. The current editorial reviews a recent study related to the in-vivo use of PegIFN-α using single-cell RNA sequencing (scRNA-seq) technology. PegIFN-α reverts the transcriptome profile of treated samples close to that of the healthy population, diminishing the pro-inflammatory genes and 'inflammatory scores' which will be important for the HBV-cure program.
Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement
Authors: Stephan Petersenn, Maria Fleseriu, Felipe F. Casanueva, Andrea Giustina, Nienke Biermasz, Beverly M. K. Biller, Marcello Bronstein, Philippe Chanson, Hidenori Fukuoka, Monica Gadelha, Yona Greenman, Mark Gurnell, Ken K. Y. Ho, Jürgen Honegger, Adriana G. Ioachimescu, Ursula B. Kaiser, Niki Karavitaki, Laurence Katznelson, Maya Lodish, Dominique Maiter, Hani J. Marcus, Ann McCormack, Mark Molitch, Christopher A. Muir, Sebastian Neggers, Alberto M. Pereira, Rosario Pivonello, Kalmon Post, Gerald Raverot, Roberto Salvatori, Susan L. Samson, Ilan Shimon, Joanna Spencer-Segal, Greisa Vila, John Wass, Shlomo Melmed
Journal: Nature Reviews Endocrinology (2023)
Cardio-Obstetrics and Heart Failure
Authors: Ersilia M. DeFilippis, Catriona Bhagra, Jillian Casale, Patricia Ging, Francesca Macera, Lynn Punnoose, Kismet Rasmusson, Garima Sharma, Karen Sliwa, Sara Thorne, Mary Norine Walsh, Michelle M. Kittleson
Journal: JACC Heart Failure (2023)
Exploring the impact of severity in hepatic fibrosis disease on the intrahepatic distribution of novel biodegradable nanoparticles targeted towards different disease biomarkers
Authors: Arunpandian Balaji, Craig A. Bell, Zachary H. Houston, Kim R. Bridle, Berit Genz, Nicholas L. Fletcher, Grant A. Ramm, Kristofer J. Thurecht
Journal: Biomaterials (2023)

Nanoparticle-based drug delivery systems (DDS) have shown promising results in reversing hepatic fibrosis, a common pathological basis of chronic liver diseases (CLDs), in preclinical animal models. However, none of these nanoparticle formulations has transitioned to clinical usage and there are currently no FDA-approved drugs available for liver fibrosis. This highlights the need for a better understanding of the challenges faced by nanoparticles in this complex disease setting. Here, we have systematically studied the impact of targeting strategy, the degree of macrophage infiltration during fibrosis, and the severity of fibrosis, on the liver uptake and intrahepatic distribution of nanocarriers. When tested in mice with advanced liver fibrosis, we demonstrated that the targeting ligand density plays a significant role in determining the uptake and retention of the nanoparticles in the fibrotic liver whilst the type of targeting ligand modulates the trafficking of these nanoparticles into the cell population of interest - activated hepatic stellate cells (aHSCs). Engineering the targeting strategy indeed reduced the uptake of nanoparticles in typical mononuclear phagocyte (MPS) cell populations, but not the infiltrated macrophages. Meanwhile, additional functionalization may be required to enhance the efficacy of DDS in end-stage fibrosis/cirrhosis compared to early stages.
Economic evaluations of whole-genome sequencing for pathogen identification in public health surveillance and health-care-associated infections: a systematic review
Authors: My Tran, Kayla S Smurthwaite, Son Nghiem, Danielle M Cribb, Alireza Zahedi, Angeline D Ferdinand, Patiyan Andersson, Martyn D Kirk, Kathryn Glass, Emily Lancsar
Journal: The Lancet Microbe (2023)

Whole-genome sequencing (WGS) has resulted in improvements to pathogen characterisation for the rapid investigation and management of disease outbreaks and surveillance. We conducted a systematic review to synthesise the economic evidence of WGS implementation for pathogen identification and surveillance. Of the 2285 unique publications identified through online database searches, 19 studies met the inclusion criteria. The economic evidence to support the broader application of WGS as a front-line pathogen characterisation and surveillance tool is insufficient and of low quality. WGS has been evaluated in various clinical settings, but these evaluations are predominantly investigations of a single pathogen. There are also considerable variations in the evaluation approach. Economic evaluations of costs, effectiveness, and cost-effectiveness are needed to support the implementation of WGS in public health settings.
Incidence of Etiology-specific Hepatocellular Carcinoma: Diverging Trends and Significant Heterogeneity by Race and Ethnicity
Authors: Paulo S. Pinheiro, Patricia D. Jones, Heidy Medina, Hannah M. Cranford, Tulay Koru-Sengul, Tim Bungum, Robert Wong, Erin N. Kobetz, Katherine A. McGlynn
Journal: Clinical Gastroenterology and Hepatology (2023)

Background & Aims The main causes of hepatocellular carcinoma (HCC) include chronic hepatitis C and B viral infections (HCV, HBV), NAFLD, alcohol-related disease (ALD). Etiology-specific HCC incidence rates and temporal trends on a population-basis are needed to improve HCC control and prevention. Methods All 14,420 HCC cases from the Florida statewide cancer registry were individually linked to data from the hospital discharge agency and the viral hepatitis department to determine the predominant etiology of each case diagnosed during 2010–2018. Age-adjusted incidence rates (AAIR) were used to assess the intersection between etiology and detailed race-ethnicity. Etiology-specific temporal trends based on diagnosis year were assessed using Joinpoint regression. Results HCV remains the leading cause of HCC among men, but since 2017 NAFLD-HCC is the leading cause among women. HCV-HCC AAIRs are particularly high among US-born minority men, including Puerto Rican (10.9 per 100,000), African American (8.0 per 100,000), and US-born Mexican American men (7.6 per 100,000). NAFLD is more common among all Hispanics and Filipinos, HBV-HCC among Asian and Haitian Black men. HCV-HCC surpasses HBV-HCC in Asian women. ALD-HCC is high among specific Hispanic male groups. Population-based HCV-HCC rates experienced a rapid decline since 2015 (-9.6% annually), while ALD-HCC (+6.0%) and NAFLD-HCC (+4.3%) are rising (p<0.05). Conclusions New directly acting anti-viral drugs have impacted rates of HCV-HCC, offsetting important increases in both ALD- and NAFLD-HCC. Hispanics may be a group of concern due to higher rates for ALD- and NAFLD-HCC. HCC etiology varies remarkably and may warrant specific interventions by detailed race-ethnicity.
Consensus position statement on advancing the standardised reporting of infection events in immunocompromised patients
Authors: Benjamin W Teh, Malgorzata Mikulska, Dina Averbuch, Rafael de la Camara, Hans H Hirsch, Murat Akova, Luis Ostrosky-Zeichner, John W Baddley, Ban Hock Tan, Alessandra Mularoni, Aruna K Subramanian, Ricardo M La Hoz, Tina Marinelli, Peter Boan, Jose Maria Aguado, Paolo A Grossi, Johan Maertens, Nicolas J Mueller, Monica A Slavin
Journal: The Lancet Infectious Diseases (2023)
Towards an equitable people-centred health system for Spain
Authors: Helena Legido-Quigley, Itxaso Berrojalbiz, Manuel Franco, Montserrat Gea-Sánchez, Sara Jaurrieta, Muriel Larrea, Sergio Minue, Javier Padilla, Jose Maria Valderas, Tomas Zapata
Journal: The Lancet (2023)
Chest Pain, Bundle Branch Block, and Wide Complex Tachycardia: Is Three a Company or Crowd?
Authors: Sophia Y. Xiao, Nora Goldschlager, Matthew S. Durstenfeld
Journal: Circulation (2023)

A 70-year-old man without previous cardiac history developed sudden onset epigastric pain, nausea, and vomiting while watching television at home.In the emergency department 30 minutes after symptom onset, his blood pressure was 102/75 mmHg, oxygen saturation was normal (98%), and high-sensitivity troponin-I was elevated at 89 859 ng/L (normal <14 ng/L).Two 12lead electrocardiograms were obtained 5 minutes apart because of the observation that patient had developed a new rhythm (Figure 1A andB).What is the most likely explanation for the presenting symptoms and ECG in Figure 1B?Please turn the page to read the diagnosis.
Highlights From the <i>Circulation</i> Family of Journals
Authors: Toru Kondo, Karola Jering, Pardeep Jhund, S Anand, Akshay Desai, Carolyn Lam, Aldo Maggioni, Felipe Martinez, Milton Packer, Mark Petrie, Marc Pfeffer, Margaret Redfield, Jean Rouleau, Dirk Van Veldhuisen, Faiez Zannad, Michael Zile, Scott Solomon, John Mcmurray, Luisa Brant, Antônio Ribeiro, Marcelo Pinto-Filho, Jelena Kornej, Sarah Preis, Jessica Fetterman, Oseiwe Eromosele, Jared Magnani, Joanne Murabito, Martin Larson, Emelia Benjamin, Antonio Ribeiro, Honghuang Lin, Jian Chee, Germaine Pua, Michelle Loo, Wai Kui, An-An Moy, Vivian Hii, Chee-Tang Lee, Jennifer Chin, Desiree-Faye Bryant, Chi-Hang Toh, Stuart Cook, ; Richards, Thu-Thao Le, Calvin Chin, Suzanne Arnold, Pratik Manandhar, Sreekanth Vemulapalli, Andrew Vekstein, Andrzej Kosinski, John Carroll, Vinod Thourani, Michael Mack, David Cohen
Journal: Circulation (2023)

Highlights from the Circulation family of journals during July cover a range of topics.Predictors of stroke among patients with heart failure and preserved ejection fraction but without atrial fibrillation are evaluated in Circulation: Heart Failure.The risk associated with an artificial intelligence-based analysis of biological age derived from ECG with outcomes is reported in Circulation: Cardiovascular Quality and Outcomes.The effect of diabetes on myocardial fibrosis assessed by cardiac magnetic resonance imaging in patients with hypertension is explored in Circulation: Cardiovascular Imaging.Reasons for improvements in transcatheter aortic valve replacement outcomes over time are explored in Circulation: Cardiovascular Interventions.
Response by Aronsen et al to Letter Regarding Article, “Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure”
Authors: Jan Magnus Aronsen, Jonas Skogestad, Ingrid Albert, Arne Olav Melleby, Cathrine R. Carlson
Journal: Circulation (2023)